1. Field of the Invention
This invention relates to sequential chemical reactions of which the polymerase chain reaction (PCR) is one example. In particular, this invention addresses methods and apparatus for performing chemical reactions simultaneously in a multitude of reaction mixtures and independently controlling the reaction in each mixture.
2. Description of the Prior Art
PCR is one of many examples of chemical processes that require a high level of temperature control of reaction mixtures with rapid temperature changes between different stages of the procedure. PCR itself is a process for amplifying DNA, i.e., producing multiple copies of a DNA sequence from a single strand bearing the sequence. PCR is typically performed in instruments that provide reagent transfer, temperature control, and optical detection of the product in a multitude of reaction vessels such as wells, tubes, or capillaries. The process includes a sequence of stages that are temperature-sensitive, different stages being performed at different temperatures and the temperature sequence being repeated in successive cycles.
While PCR can be performed in any reaction vessel, multi-well reaction plates and microfluidics devices with multiple channels are the reaction vessels of choice so that many strands of DNA can be replicated simultaneously. In many applications, PCR is performed in “real-time” and the reaction mixtures are repeatedly analyzed throughout the process, by the detection of light from fluorescently-tagged species in the reaction medium. In other applications, DNA is withdrawn from the medium for separate amplification and analysis. In multiple-sample PCR processes, a preferred arrangement is one in which each sample occupies one well of a multi-well plate or one channel of a multi-channel microfluidics device, and all samples in the plate or the microfluidics device are simultaneously equilibrated to a common thermal environment at each stage of the process.
Using a 96-well microplate with a sample in each well as an example, the plate is typically placed in contact with a metal block that is heated and cooled either by a Peltier heating/cooling apparatus or by a closed-loop liquid heating/cooling system that circulates a heat transfer fluid through channels machined into the block. In general, however, rapid changes in temperature that are uniform across all wells or channels are still difficult to achieve.